Antidepressant drugs clinical trials

At first, Sapirstein and I found the equivalence between antidepressants and other drugs puzzling, to say the least. Why should drugs that are not antidepressants be as effective as antidepressants in treating depression To answer this question, we asked another. What do all these diverse drugs have in common that they do not share with inert placebos What do SSRIs have in common with the older tricyclic antidepressants, with other less common antidepressants, and even with tranquillizers, depressants and thyroid medication The only common factor that we were able to note was that they all produce easily noticeable side effects - the one thing that was lacking in Merck s new treatment for depression. Placebos can also produce side effects, but they do so to a much lesser extent than active medication. Clinical trials show that whereas the therapeutic benefits of antidepressants are relatively small when compared to placebos, the difference in side effects is substantial.7... 

In this chapter we have looked at the results of published clinical trials of antidepressant medication. The published studies showed a significant, but surprisingly small, effect of antidepressants over placebos. But as I noted at the beginning of the chapter, those data represented only the beginning. As I later discovered, there were also studies that had been withheld from publication. These unpublished studies were clinical trials that did not show a significant benefit for drugs over placebo medication - trials that the drug companies withheld... 

There were indeed clinical trials of antidepressants that we had not included in our meta-analysis, and there was also a meta-analysis of those other trials that had used some of the same methods we had used. It showed the same results that we had reported. The difference between drug and placebo in published trials of antidepressants was modest at best.3 Still, the controversy continued. 

Moore s idea of analysing the data that had been sent to the FDA seemed brilliant, and I proposed that we work on it together. So we began. Moore wrote to the FDA invoking the Freedom of Information Act and requested the medical and statistical reviews of every placebo-controlled clinical trial for the treatment of depression by what, at that time, were the six most widely used new-generation antidepressant drugs Prozac, Seroxat (Paxil in... 

Our first published report of the FDA data was accompanied by nine expert commentaries, some of them by researchers who had conducted clinical trials of antidepressant medication. Although there were vast differences in interpretation, this time there were no doubts about the accuracy of our analysis. Some commentators argued that our analysis had actually overestimated the real effect of antidepressants. Others argued that the clinical trials sponsored by the drug industry are flawed and that they may underestimate the actual benefit of antidepressants. But all... 

In our meta-analysis, more than half of the clinical trials submitted to the FDA showed no difference between drug and placebo. Most reviewers of the clinical-trials literature have not had access to unpublished studies and may not even know of their existence. But the FDA and other regulatory agencies around the world knew of these data. Nevertheless, their existence is not even mentioned in the product labels, information leaflets and official Summaries of Product Characteristics (SPC) of most antidepressants. 

These continuation trials tell a very different story from that told by relapse-prevention trials. They show that there is little difference between antidepressant and placebo even when the clinical trial is extended over a longer period of time. Across the eight continuation trials that have been published, 79 per cent of patients on placebo and 93 per cent of patients on active medication remained well throughout the treatment period. In these long-term studies, placebo treatment was 95 per cent as effective as drug treatment. The authors of a meta-analysis of these trials concluded that the widely held - and probably erroneous - belief that the placebo response in depression is short-lived appears to be based largely on intuition and perhaps wishful thinking .17... 

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